The octapeptide hormone, angiotensin II, has been demonstrated to exert a profound influence on various aspects of the central neural control of body fluid and blood pressure regulation. Acting upon the brain either from the circulation or directly, exogenous angiotensin II increases blood presssure by sympathetic activation and vasopressin release, increases body fluid volumes by fluid retention consequent to vasopressin release and also stimulates thirst and sodium appetite. Intracranial injection of various elements of the renin-angiotensin system reproduces the effects of angiotensin II on the brain. This suggests that the specific agents required for production of angiotensin II from precursors are present within the brain. Biochemical analysis has confirmed the presence of all the components of a renin-angiotensin system in neural tissue and has led to the suggestion that the brain possesses a reninangiotensin system independent of, and physically isolated by, the blood-brain barrier from the peripheral renin-angiotensin system. The focus of the proposed studies will be to advance current understanding of brain angiotensin relations with two principal approaches. First, the studies will utilize high performance liquid chromatography (HPLC) to characterize angiotensin-like materials prior to radioimmunoassay (RIA) quantification. This will eliminate many of the vagueries of data in the past which have relied solely on immunoreactive measurements. The second objective is an examination of the effects of physiological stimuli which, on the basis of known actions of angiotensin on the brain, may activate brain angiotensin production. Currently, information available in this area is sparse. The technique of push-pull perfusion will be employed in this area of the study. This technique will permit a localized analysis of brain angiotensin release. Studies will be performed to assess angiotensin release at various brain sites selected on the basis of published immunohistochemical data and preliminary data. Efforts will be made to characterize which of the possible angiotensin peptides is/are responsible for immunoreactivity by HPLC separation of angiotensin in perfusates. Experiments will be performed to determine whether the origin of angiotensin in push-pull perfusates is neuronal. Finally this information, together with informaton in existence concerning the actions of exogenous angiotensin on the brain will be used to focus studies on the possible physiological relevance of brain angiotensin by attempting to influence brain angiotensin release by stimuli aimed at activating physiological mechanisms in which brain angiotensin may participate.